Retention Time and Ion Abundance Ratio of 8 Common Drugs (Poisons) by LC-MS/MS Qualitative Analysis / 法医学杂志

Objective To investigate the maximum allowable deviations of retention time and ion abundance ratio of the 8 common drugs (poisons) from 3 categories, poisons (methamphetamine, morphine, ketamine), benzodiazepines (estazolam, midazolam, diazepam, clonazepam) and barbiturates (phenobar-bital) in blood, by liquid chromatograpy-tandem mass spectrometry (LC-MS/MS) in forensic toxicology analysis. Methods The deviations of retention time and ion abundance ratio at 7 low mass concentrations, limit of detection (LOD), 2LOD, limit of quantitation (LOQ), 1.5LOQ, 2LOQ, 4LOQ and 6LOQ, were tested by LC-MS/MS after liquid-liquid extraction under the conditions of two chromatographic columns and three chromatographs. Results The deviation of absolute retention time of 98.11% of 8 drugs (poisons) in the blood samples was within the range of ± 0.05 min, and that of the relative retention time of 96.21% was within the range of±0.4%. The maximum deviation of the ion abundance ratio was highly correlated with the mass concentration. When the mass concentration of drugs (poisons) was LOQ or above, more than 95% of the absolute deviation and relative deviation of the ion abundance ratio were in the range of±25% and±40%, respectively; when the mass concentration was below LOQ, the range could be expanded to±35% and±50%, respectively. Conclusion It is recommended for the determination range of the absolute retention time deviation of 8 common drugs (poisons) to be±0.1 min and that of the relative retention time deviation to be±1.0%. The determination range of absolute deviation of the ion abundance ratio should be±25% when the mass concentration is LOQ or above, and the relative deviation should be±40%. When the mass concentration is below LOQ, the deviation determination range can be expanded to±35% and±50%, respectively.

Targeting neuropilin-1 interactions is a promising anti-tumor strategy / 中华医学杂志(英文版)

Neuropilins (NRP1 and NRP2) are multifunctional receptor proteins that are involved in nerve, blood vessel, and tumor development. NRP1 was first found to be expressed in neurons, but subsequent studies have demonstrated its surface expression in cells from the endothelium and lymph nodes. NRP1 has been demonstrated to be involved in the occurrence and development of a variety of cancers. NRP1 interacts with various cytokines, such as vascular endothelial growth factor family and its receptor and transforming growth factor β1 and its receptor, to affect tumor angiogenesis, tumor proliferation, and migration. In addition, NRP1+ regulatory T cells (Tregs) play an inhibitory role in tumor immunity. High numbers of NRP1+ Tregs were associated with cancer prognosis. Targeting NRP1 has shown promise, and antagonists against NRP1 have had therapeutic efficacy in preliminary clinical studies. NRP1 treatment modalities using nanomaterials, targeted drugs, oncolytic viruses, and radio-chemotherapy have gradually been developed. Hence, we reviewed the use of NRP1 in the context of tumorigenesis, progression, and treatment.

Ion Abundance Ratios of Qualitative Analysis by GC-MS of 4 Common Drugs （Poisons / 法医学杂志

Objective To investigate the maximum allowable deviation of ion abundance ratios of characteristic fragment ions in common drugs （poisons） in blood by gas chromatography-mass spectrometry （GC-MS） method. Methods Four common drugs （poisons） （dichlorvos, phorate, diazepam and estazolam） were detected by GC-MS full scan mode after liquid-liquid extraction in two laboratories and under three chromatographic conditions. The deviations of ion abundance ratios of the four common drugs （poisons） in marked blood samples with concentrations of 0.5, 1.0, 2.0, 5.0 and 10.0 μg/mL were analyzed. At the same time, the false negative rates of ion abundance ratios were analyzed when the mass concentration was limit of detection （LOD）, 2LOD, limit of quantitation （LOQ） and 2LOQ, and the false positive rates of ion abundance ratios were analyzed with blank blood samples. Results Under the two laboratories, four common drugs （poisons） and three kinds of chromatography conditions, the differences in deviations of the ion abundance ratios of marked blood samples were not statistically significant （P>0.05）. More than 95% of the absolute deviations of the ion abundance ratios of the marked blood samples were within the range of ±10%, and more than 95% of the relative deviations were within the range of ±25%. In cases of low concentration （concentration less than 2LOQ） or low signal to noise ratio （3-15）, the false negative rate was less than 5% and the false positive rate was 0% when the relative deviation was greater than 50%. Conclusion The absolute deviations of ion abundance ratios of four common drugs （poisons） in marked blood samples are advised to have a determination range within ±10%, and the determination range of relative deviations within ±25%.

Retention Time of Four Common Poisons (Drugs) by GC-MS Qualitative Analysis / 法医学杂志

Objective To investigate the maximum allowable deviation of retention time (RT) or relative retention time (RRT) between the common poisons (drugs) and standard solvent by gas chromatography-mass spectrometry (GC-MS).Methods After pretreatment with liquid-liquid extraction, four common poisons (drugs) —dichlorvos, phorate, diazepam and estazolam—were detected by full scan mode GC-MS.RT and RRT were analyzed according to combined uncertainty and expanded uncertainty. Results The expanded uncertainty of RT and RRT were 6.0× lO-4-14.1×l0-3 and 2.5 ×l0-6-5.9× lO-5 (k=3), respectively.The RT of poisons (drugs) was relatively stable in blood samples with different mass concentrations.Among dichlorvos, phorate, diazepam and estazolam, the absolute deviation and relative deviation of RT were≤0.03 min and≤0.4％, respectively, and those of RRT were≤0.003 min and≤0.3％, respectively.Conclusion The maximum allowable deviations of RT and RRT for common poisons (drugs) in blood samples are recommended to be±0.05 min and±0.5％.

Confirming Indicators of Qualitative Results by Chromatography-mass Spectrometry in Biological Samples / 法医学杂志

Because of the exist of complex matrix, the confirming indicators of qualitative results for toxic substances in biological samples by chromatography-mass spectrometry are different from that in non-biological samples. Even in biological samples, the confirming indicators are different in various application areas. This paper reviews the similarities and differences of confirming indicators for the analyte in biological samples by chromatography-mass spectrometry in the field of forensic toxicological analysis and other application areas. These confirming indicators include retention time （RT）, relative retention time （RRT）, signal to noise （S/N）, characteristic ions, relative abundance of characteristic ions, parent ion-daughter ion pair and abundance ratio of ion pair, etc.